This study is a randomized, prospective, multicenter trial to determine the safety and efficacy of cryotherapy of the retina in the treatment of retinopathy of prematurity (ROP). It is designed to determine if cryotherapy will prevent the progression of the acute disease to blindness and severe visual disability (Grade III cicatricial retrolental fibroplasia (RLF) or worse by Reese's Classification). Since the number of infants with Stage 3+ ROP at any one nursery center is relatively small it is only by a multi-center randomized trial that the question of the efficacy of cryotherapy can be definitively answered. Data on ROP will be accumulated prospectively on approximately 6,000 premature infants from twenty nursery centers from which approximately 300 patients will receive cryotherapy treatment. This registry of small birth weight infants will be utilized for descriptive analyses with regard to the development of ROP to identify factors such as location, extent, stage, presence or absence of plus disease which play a role in the prognosis of infants with ROP. An adequate test of the efficacy of cryotherapy requires that infants less than 1251 grams be followed to identify as treatment candidates all infants in which the disease progresses to Stage 3+ ROP and who have more than 5 contiguous clock hours of disease. Approximately 80% of the 300 Stage 3+ ROP infants who reach the threshold for treatment are expected to have disease which progresses symmetrically in both eyes. One eye will be treated and the other eye will remain untreated with the treated eye selected at random. The remaining 20% of the infants will have one eye (the first eye to reach threshold) randomly allocated to treatment with cryotherapy or control. The study consists of a six month preparation phase. Enrollment for this study will extend over a 2 1/2 year period with follow-up of each infant for one year. Efficacy of cryotherapy will be judged by the comparison of the treated versus the control eyes at three months and one year of follow-up. The Study Coordinating Center will be located at the University of Texas Health Science at Houston, Texas. The Study Headquarters will be located at The Oregon Health Sciences University at Portland, Oregon, under the direction of Earl A. Palmer, M.D.